Research proposed aims at establishing a norm for specific macromolecular constituents of epithelial and stromal elements in the cochleas of animals with normal hearing. The importance of these components for normal hearing and for development of presbyacusis will be assessed by comparing their relative abundance in aging gerbils exposed to different levels of noise. Because a large potential difference exists between endolymph and perilymph, constituents that establish and maintain essential ionic gradients will be analyzed. Transport mediators such as (Na+ +K+)-ATPase and carbonic anhydrase will be localized immunocytochemically in the cochlea of young gerbils with normal hearing and the results compared with those from animals suffering noise-induced and/or age-related hearing loss. Age-related changes in other functionally important enzymes and proteins such as superoxide dismutase, calmodulin and cytoskeletal constituents will be assessed using similar methods. Because the chemical composition of the glycocalyx on the surface of epithelial cells varies between cells of differing functions, investigation into the nature of the glycocalyx of cochlear cells is proposed. This will entail staining cochleas from young and old animals with labeled lectins having specific affinity for different sugars or sugar sequences in glycoconjugates. Connective tissue and basement membrane components comprise another category of cochlear macromolecules that undoubtedly contribute to auditory function. Stromal and basement membrane constituents to be localized and compared in a series of aging gerbils are types I-IV collagen, elastin, laminin and fibronectin and the diverse proteoglycans of the ground substance. A significant aspect of the proposed research is the ability to relate the histochemical results on each cochlea to the morphologic, audiologic and physiologic data obtained in Projects 1, 3 and 4 on the same cochlea.